ECH 3602

Toxicological studies
(Hazardous properties of processing materials)

By
Dr. Mus’ab Abdul Razak

9/28/2019 1
 Hazardous properties
Exposure Toxic hazards:
measurements: • Systemic poisons Material Process
➢ PEL • Asphyxiants,
➢ TLV • Carcinogens, hazards hazards
➢ TLV-TWA, • Mutagens,
➢ TLV-STEL, • Teratogens,
➢ TLV-C • Irritants,
➢ BEI • Allergens, Toxicity Overpressure
• Sensistizers
• Anaesthetics
Flammability: • Narcotics Fire hazards:
• Flash point • Fire tetrahedron
• AIT Flammability Fire • Flash point
• MIE • LEL
• LFL Reactivity hazards: • UEL
• LFL • Exothermic reactions • Ignition source
• Adiabatic • Effects of material
compression properties
• Reaction rates &
Reactivity Explosion • Detonation
Basic storage temperature • Deflagration
requirements: • Explosion potential of • Confine explosion
Flammables molecular functional • Blast damage
• Oxidisers group • TNT equivalency
• Reducing Incompatibility LOC • TNO Multi Energy method
agents • VCE
• Acids
• Bases Corrosive hazards:
• Alkalis • Acids
• etc. • Bases Corrosivity Noise
• halogens
INTRODUCTION TO
TOXICOLOGICAL
STUDIES
 The Study Of Poisons
INTRODUCTION TO TOXICOLOGY

HAZARDOUS WASTE
START DATE:______________
AMOUNT:__________________
CONTENTS:________________
HANDLE WITH CARE
 Introduction to toxicology

“ALL THINGS ARE POISONS, OR

THERE IS NOTHING WITHOUT
POISONOUS QUALITIES. IT IS ONLY
THE DOSE WHICH MAKES A THING
POISON.”

PARACELSUS
(1493 - 1541)
 What is Toxicology

• Involves all aspect of adverse effect of

chemicals on living system

• Those effects which are damaging to either

the survival or normal function of the
individual
 Terminologies

Chemical/physical agents Toxicant Vapor, dust, fibre, noise, radiation

Poison – plant or
animal origin
Toxin Bufotoxin, endotoxin

Describe the effect – acute or

Property of agents Toxicity chronic, degree of harm

Qualitative & Quantitative - Toxicology State of toxicant

study effect on biological system Dose vs response
Reversible & Irreversible effect

Likelihood of damage based Toxic hazard Due to handling, transport and

on exposure other physical factor of usage

8
 An Individual View

The sensitivity of the individual differentiates a

poison from a remedy. The fundamental
principle of toxicology is the individual’s
response to a dose
S. G. Gilbert

Age Gender Genetics Pre-condition Diet

 Toxicity vs Hazard

Two chemicals can possess the same degree of

toxicity, but present different degrees of
hazard.

Example:
Odourless and non-irritating vs pungent odour

The chemical with warning properties may

present a lesser degree of hazard.
 Toxic Hazard/Risk

• Toxic hazard/risk is the likelihood of

damage to biological organisms based on
exposure due to transport and other
physical factors of usage

• Toxic hazard of a substance can be reduced

by the application of appropriate industrial
hygiene techniques

• However, toxicity cannot be changed

 Introduction

The chemical engineers must be knowledgeable

about
• The way toxicants enter biological organisms
• The ways toxicants are eliminated from
biological organisms
• The effects of toxicants on biological organisms
• Methods to prevent or reduce the entry of
toxicants into biological organisms
ROUTE OF ENTRY AND
EXPOSURE
 Route entry

BRAIN
TOXIN
RESPIRATORY
Inhaled Toxins Can SYSTEMS
Quickly Travel to Vital
Organs and the Brain
HEART
Causing Either Acute
or Chronic Effects.
STOMACH
LIVER
INTESTINE
 Route entry
• Ingestion – Food & Drink
• Mucus swallow – Airborne particle Absorption
Rate & selectivity
Gastrointestinal • Type of chemical
(GI) • MW
• Size & shape
• Acidity
Upper respiratory – • Susceptibility
React to water soluble toxicant
e.g. halide, oxides, hydroxides
Respiratory Dissolution
system
Lower respiratory Particle deposition
React with alveoli wall and
produce corrosive or toxic
Permeability
• Location
Skin
• Dermal absorption • Hydration
• Injection
• Cut, mechanical injection Absorption
Predicted fractional deposition of inhaled particles in the
nasopharyngeal, tracheobronchial, and alveolar region on the
human respiratory tract during nose breathing

• Filtering
respiratory

• Heating
Upper

• Dehumidifying
Particle > 5 m
MUCUS

Particle : 2- 5 m
Lower respiratory

Particle < 1 m
Route entry - skin
 How Toxicants Enter Organism

• Inhalation (mouth or nose to lungs) then into

blood
• Ingestion (mouth to stomach) then into blood
• Injection (cuts, punctures in skin) then into blood
• Dermal absorption (through skin) then into
blood

Of the four routes of entry, inhalation and dermal

absorption are the most significant to industrial
facilities.
 Examples of occupational skin toxicity

Eczema from
cutting oil
Acne from cutting oil
Sensitization to dichromate

Atopic irritant dermatitis

Leukoderma from rubber
antioxidants
Beryllium granulomas

Burn from ethylene oxide

Hyperpigmentation from
Burn from alkali exposure Phototoxicity from lime juice mercaptobenzothiazole
She died of mercury
poisoning at the age of 48 due
to accidental exposure to
theorganic mercury compound
dimethylmercury (Hg(CH3)2).

Protective gloves in use at the

time of the incident provided
insufficient protection, and
exposure to only a few drops of
the chemical absorbed through
the gloves proved to be fatal
after less than a year.
Karen Elizabeth
Wetterhahn (October 16, 1948 –
June 8, 1997) was an American
professor of chemistry at Dartmouth
College, New Hampshire who
specialized in toxic metal exposure.

Wetterhahn would recall that she had spilled one or two drops of dimethylmercury from the tip of a
pipette onto her latex-gloved hand. Not believing herself in any immediate danger, as she was taking
all recommended precautions,[5] she proceeded to clean up the area prior to removing her protective
clothing.[6] However, tests later revealed that dimethylmercury can, in fact, rapidly permeate
different kinds of latex gloves and enter the skin within about 15 seconds.[4] The exposure was later
confirmed by hair testing, which showed a dramatic jump in mercury levels 17 days after the initial
accident, peaking at 39 days, followed by a gradual decline
 Method of control

Entry route Entry Methof for control

organ
Ingestion Mouth or Enforcement of rules on
stomach eating, drinking and smoking

Inhalation Mouth or Ventilation, respirators,

nose hoods and other PPE
Injection Cuts in skin Proper PPE

Dermal absorption Skin Proper PPE

 Effects of Exposure

• ACUTE – a “one-time” event

➢ Rapid absorption of material
➢ Exposure sudden & severe
➢ Critical period for death/survival

• CHRONIC – small doses over long time

➢ Rate of intake > rate of elimination
➢ Material remains in tissue; injures
 Duration of Exposure

Effect Time Exposure pattern

Acute < 24 hrs Usually 1 exposure
Subacute 1 month Repeated doses
SubChronic 1-3 months Repeated doses
Chronic > 3 months Repeated doses
ELIMINATION &
RESPONSES TO
TOXICANTS
 Sweat

dominant
Bile
Toxic elimination
biotransformation
MW < 300
Detoxification
Urine
dominant
Excretion

Storage

Volatile

OTHERS
 Effect of toxicant on biological organism
Irreversible Reversible
(may or may not)

• Carcinogen • Dermatoxic
• Mutagen • Hemotoxic
• Reproductive • Hepatoxic
hazard • Nephrotoxic
• Teratogen • Neurotoxic
How to
determine ? • Pulmonotoxic
➢ Respiratory : Spirometer
➢ Liver & Kidney : ▪ FVC & FEV
▪ Blood Test Medical test ➢ Nervous System :
▪ Urine Test ▪ Mental status
vs
▪ EEG
Baseline study
▪ Reflexes
▪ Sensory
 Toxicological studies
Objective: To quantify effects of the suspect toxicant on a
target organism.

• Chemical composition Target/ • Single cell – for genetic study

The
• Physical state • Animal – for specific organ
toxicant Test organism

• Acute toxicity
• Chronic toxicity
Response
Period of • Latent toxicity
to be
test
monitored

• Short term effect Method of delivery

• Long Term effect Dose • Direct – dose in mg (agent)
• Single exposure range /kg(body weight)
• Multiple exposure • Gaseous airborne – ppm or
mg/m3
• Particulates – ppm or mppcf
 Dose vs Response
D-R
Curve GUIDELINES

Relative TLV
toxicity (ACGIH)

Dose
AIRBORNE
vs CONCENTRATION
Response
Probit PEL
Analysis (OSHA)

LEGAL
LD50/LC50
 Definitions
• Threshold dose suggests that there should be a dose
or exposure level below which harmful or adverse
effect are not seen in population

• Dose is the amount of chemical entering the body.

Usually given as mg of chemical/kg of body = mg/kg

• The dose is dependent upon

▪ The environmental concentration
▪ The properties of the toxicant
▪ The frequency of exposure
▪ The length of exposure
▪ The exposure pathway
 How to develop D-R Curve
Example :
• Consider and effect
of carcinogen on
human , given a
same dose some
individual will
barely get any sign
of cancer (weak or
low response)
whereas other
individuals will
terminally ill cancer
(high response).

• The biological
response can be
plotted we run for
big population.
 Response – Log Dose Curve

For convenience, the response is plotted versus the

logarithm of the dose
• If the response of the interest is death or lethality =
lethal dose curve, LD/ LC = lethal concentration (gas)
• If the response to the chemical or agent is minor or
irreversible = effective dose, ED
• If the response to the agent is toxic (not lethal but
irreversible) = toxic dose, TD
 Lethal dosage
The LD50 is the dosage, when The LC50 is the
administrated to laboratory concentration of a
animals, results in 50% fatalities. material that, normally
The expression is made in express as parts per
milligrams of the substance million (ppm) by
administered per body weight of volume, that when
the animal expressed in administrated to
kilograms (mg/kg). LD50 laboratory animals, kill
typically refers to dermal half of them during the
dosages. period of exposure.
LC50 typically refers to
When extrapolated to humans,
airborne dosages.
the lethal dose of an average
person who weighs W kilograms
is LD50 x W.
 Threshold limit values
Conversion: Formerly
TLV-C :
- Any part of the
mg/m3 to ppm D-R known as MAC working exposure
Curve TLV-TWA :
22.4 𝑇 1 mg - 40 hr/week
Cppm = Relative ( 3) TLV - No adverse effect
𝑀𝑊 273toxicity𝑃 m TLV- STEL :
(ACGIH) - exposure < 15 min
Dose - No irritation, toxic
vs AIRBORNE effect, chronic
CONCENTRATION tissue damage,
Response narcosis
Probit
PEL
GUIDELINES
Analysis
IDLH
(OSHA)
LD50/LC50
LEGAL
 Model for D-R curve
Objective:
To transform sigmoid shape of D-R curve into straight D-R

line using std curve fitting technique. Curve

Relative TLV
toxicity
(ACGIH)
• The probit (probability unit) Dose
method is very common for single vs
exposure computational. Response
• The probit variable Y is related to Probit PEL
the probability P by this equation: Analysis (OSHA)

LD50/LC50

1 Y −5
u2
P= 1  exp( − )du
(2 ) 2  2
 Conversion of Probit to percentage
% 0 1 2 3 4 5 6 7 8 9
0 - 2.67 2.95 3.12 3.25 3.36 3.45 3.52 3.59 3.66
10 3.72 3.77 3.82 3.87 3.92 3.96 4.01 4.05 4.08 4.12
20 4.16 4.19 4.23 4.26 4.29 4.33 4.36 4.39 4.42 4.45
30 4.48 4.50 4.53 4.56 4.59 4.61 4.64 4.67 4.69 4.72
40 4.75 4.77 4.80 4.82 4.85 4.87 4.90 4.92 4.95 4.97
50 5.00 5.03 5.05 5.08 5.10 5.13 5.15 5.18 5.20 5.23
60 5.25 5.28 5.31 5.33 5.36 5.39 5.41 5.44 5.47 5.50
70 5.52 5.55 5.58 5.61 5.64 5.67 5.71 5.74 5.77 5.81
80 5.84 5.88 5.92 5.95 5.99 6.04 6.08 6.13 6.18 6.23
90 6.28 6.34 6.41 6.48 6.55 6.64 6.75 6.88 7.05 7.33
% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
99 7.33 7.37 7.41 7.46 7.51 7.58 7.65 7.75 7.88 8.09
 Probit Variable Y

Y = k1 + k 2 ln V
k1, k2 Probit parameters
V Causative factor represents the dose
 Probit: Toxic Release

Causative variable, V = ƩCaT Probit Parameters

(C is concentration in ppm, T is time in
minutes)
Type of Injury a k1 k2
Ammonia Death 2.0 -35.9 1.85
Carbon Monoxide Death 1.0 -37.98 3.7
Chlorine Death 2.0 -8.29 0.92
Ethylene Oxide Death 1.0 -6.19 1.0
Hydrogen Chloride Death 1.0 -16.85 2.0
Nitrogen Dioxide Death 2.0 -13.79 1.4
Phosgene Death 1.0 -19.27 3.69
Propylene Oxide Death 2.0 -7.42 0.51
Sulfur Dioxide Death 1.0 -15.67 1.0
Toluene 2.5 -6.79 0.41
 Probit: Fire and Explosion
Type of injury or damage Causative Probit parameters
variable (V) k1 k2
Fire
Burn deaths from flash fire t e Ie4 / 3 /10 4 -14.9 2.56
Burn deaths from pool -14.9 2.56
burning
t Ie4 / 3 /10 4
Explosion
Deaths 
from lung po -77.1 6.91
haemorrhage
Eardrum ruptures  po -15.6 1.93
Deaths from impact J -46.1 4.82
Injuries from impact J -39.1 4.45
Injuries from flying J -27.1 4.26
fragments
Structural damages p0 -23.8 2.92
Glass breakage p0 -18.1 2.79
Here, te is the effective time duration (s), t is the time duration of pool burning (sec), Ie is the effective
radiation intensity (W/m2), I is the radiation intensity from pool burning (W/m2), te is the effective time
duration (s), po is peak overpressure (N/m2), J is impulse (Ns/m2), C is concentration (ppm) and T is
time interval (min).
Question 2.2 (Crowl & Louvar, 2002)
The effect of rotenone on macrosiphoniella sanborni sp. was investigated. Rotenone
was applied in a medium of 0.5% saponin, containing 5% alcohol. The insects were
examined and classified one day after spraying. The obtained date were:
Dose (mg/l) Number of insects Number affected
10.2 50 44
7.7 49 42
5.1 46 24
3.8 48 16
2.6 50 6
0 49 0

From the given data, plot the percentage of insects affected versus the natural
logarithm of dose
Convert the data to a probit variable, and plot the probit versus the natural
logarithm of the dose. If the results is linear, determine a straight line that fits the
data. Compare the probit and number of insects affected predicted by the straight
line fit to the actual data.
OTOH, conversion from probits to percentage
is given by (Equa.6)

 Y −5  Y − 5 
P = 501 + erf  
 Y − 5  2 

erf the error function of Y

 Relative toxicity
Which one is more toxic at high D-R
Curve
dose? Relative TLV
toxicity (ACGIH)
Dose
vs
Response
Probit PEL
Analysis
(OSHA)

LD50/LC50

Toxicant A is more toxic at high

doses.
 Scale of Relative Toxicity
Hodge-Sterner table for degree of toxicity
EVALUATING
EXPOSURE
 Tragedies that changed the safety movement
(related to toxic materials)

Bhopal
Asbestos Tragedy
Menace ( 1964) (1984)
Hawk’s Nest (1930’S)
 Evaluating exposure to toxicants
The evaluation phase determines Special attention must be
the extent and degree of Volatile directed toward preventing
toxicant by
employee exposure to monitoring and controlling low
toxicants and physical concentrations of toxic
hazards in the gases.
workplace
environment.
Evaluating
Vessel
Filling Exposure Dust
to

During the evaluation

study, the likelihood of
large and small leaks must
be considered; Toxic
Two type of evaluation:
Large → high concentration → Acute vapour
• Continuous or frequent
Small → low concentration → Chronic
• Periodic sampling
 Evaluating exposure to toxicants
How do you know the control Control measures:
• Wet method
measures are effective? • Ventilation
• Enclosure
• LEV
Samples • PPE
collection

Compare to
Determine
acceptable
the TLVs,
occupational
workers’ PELs,
health
exposure IDLH
standards,
 Evaluating exposure to toxicants by monitoring
Direct method – continuously monitoring the air concentration of
toxicant on-line in a work environment.

1 𝑡𝑤 C(t) concentration of toxicant in the air

TWA = න 𝐶 𝑡 𝑑𝑡 tw the worker shift time in hours
8 0

Continuous
or 𝐶1 𝑇1 + 𝐶2 𝑇2 + ⋯ 𝐶𝑛 𝑇𝑛
TWA =
Intermittent ? 8 ℎ𝑟

Drawbacks:
• Workers move in-move out
• Concentration varies with locations
 Evaluating exposure to toxicants by monitoring
Multiple exposure ? Assume toxicant effect is additive

The combined exposures from multiple toxicants with

different TLV-TWAs is determined from the equation;
𝑛 n no of toxicants
𝐶𝑖 Ci concentration of chemical i
෍ with respect to the other
𝑇𝐿𝑉 − 𝑇𝑊𝐴 𝑖 toxicants
𝑖=1
(TLV-TWA)i is TLV-TWA for each
If > 1 workers are overexposed chemical species i

σ𝑛𝑖=1 𝐶𝑖 If sum of
(TLV−TWA)𝑚𝑖𝑥 = concentration of
𝐶𝑖 the toxicants in
σ𝑛𝑖=1 the mixture > this
𝑇𝐿𝑉 − 𝑇𝑊𝐴 𝑖 amount, workers
are overexposed
 Evaluating exposure to dust
Objective:
➢ To estimate the concentrations that are inhaled and
deposited in the lungs.
• Sampling methods and Special control
the interpretation of data measures will be
relevant to health required when the
hazards are relatively actual particle count
complex. (of the size range
• Industrial hygienists, specified in the
who are specialists in standards or by an
this technology, should industrial hygienist)
be consulted. exceeds 6.8 mppcf.
Determine the TLV for a uniform mixture of dusts
containing the following particles:
Type of dust Concentration TLV
(wt%) (mppcf)
Dust A 70 20.0
Dust B 30 2.7

Special control measures

will be required when
the actual particle count
(of the size range
specified in the
standards or by an
industrial hygienist)
exceeds 6.8 mppcf.
 Evaluating exposure to toxic vapour
The best procedure to determine exposures to toxic vapours is to
measure the vapour concentrations directly.

Consider the enclosed volume shown below;

𝑄𝑚 𝑅𝑔 𝑇
𝐶 𝑝𝑝𝑚 = × 106
𝑘𝑄𝑣 𝑃𝑀
Application of this equation;
1. A worker standing near a pool of volatile liquid,
2. A worker standing near an opening to a storage tank
3. A worker standing near an open container of volatile liquid.

Important assumptions:
❑ The calculated concentration is an
average concentration in the
𝑄𝑚 𝑅𝑔 𝑇 enclosure. Localized conditions
𝐶 𝑝𝑝𝑚 = × 106
𝑘𝑄𝑣 𝑃𝑀 could result in significantly higher
concentrations; workers directly
above an open container might be
➢ The non-ideal mixing exposed to higher concentrations.
factor varies from 0.1 to ❑A steady-state condition is
0.5 for most practical
assumed; that is, the accumulation
situations.
➢ For perfect mixing k = 1.
term in the mass balance is zero.
 Example

An open toluene container in an enclosure is weighed as a function of

time, and it is determined that the average evaporation rate is 0.1
g/min. The ventilation rate is 100 ft3/min. The temperature is 80°F
and the pressure is 1 atm. Estimate the concentration of toluene
vapor in the enclosure, and compare your answer to the TLV for
toluene of 20 ppm.

Solution
Because the value of k is not known directly, it must be used as a parameter.

Because k varies from 0.1 to 0.5, the

𝑄𝑚 𝑅𝑔 𝑇 concentration is expected to vary from 18.9 ppm
𝑘𝐶 𝑝𝑝𝑚 = × 106 to 94.3 ppm. Actual vapor sampling is
𝑄𝑣 𝑃𝑀 recommended to ensure that the TLV of 20 ppm
is not exceeded.
 Estimating vapourisation rate of liquid

• Liquids with high saturation vapour pressures evaporate faster.

• As a result, the evaporation rate (mass/time) is expected to be a function of
the saturation vapour pressure.
• In reality, for vaporisation into stagnant air, the vaporisation rate is
proportional to the difference between the saturation vapour pressure and
the partial pressure of the vapour in the stagnant air;

𝑄𝑚 ∝ 𝑝 𝑠𝑎𝑡 − 𝑝

𝑀𝐾𝐴 𝑝 𝑠𝑎𝑡 − 𝑝
𝑄𝑚 =
𝑅𝑔 𝑇𝐿
 Estimating vapourisation rate of liquid
𝑀𝐾𝐴 𝑝 𝑠𝑎𝑡 − 𝑝
𝑄𝑚 =
𝑅𝑔 𝑇𝐿
Used to estimate the
For many situations, vaporization rate of
Psat >> p, therefore volatile from an open
𝑀𝐾𝐴 𝑝 𝑠𝑎𝑡 vessel or from a spill of
𝑄𝑚 = liquid.
𝑅𝑔 𝑇𝐿

Used to 𝐾𝐴𝑇𝑝 𝑠𝑎𝑡

estimate the 𝐶 𝑝𝑝𝑚 = × 106
𝑘𝑄𝑣 𝑃𝑇𝐿 Mass transfer
concentration
coefficient, water
(in ppm) of a
For most situations T = TL as ref. substance,
volatile in an
K0=0.83 cm/s
enclosure
resulting from 𝐾𝐴𝑝 𝑠𝑎𝑡 𝐾 = 𝐾0
𝑀0
evaporation of 𝐶 𝑝𝑝𝑚 = × 106 𝑀
a liquid 𝑘𝑄𝑣 𝑃
A large open tank with a 5-ft diameter contains toluene. Estimate
the evaporation rate from this tank assuming a temperature of
77°F and a pressure of 1 atm. If the ventilation rate is 3000
ft3/min, estimate the concentration of toluene in this workplace
enclosure.
Required info:
• Saturation pressure
• Molecular weight
• TLV
ANALYSIS
Calculate : • Range of kCppm
✓ Pool area • Compare with TLV
✓ Evaporation rate • Estimate Qv to reduce
✓ Concentration with k as parameter concentration
Estimating Worker Exposures during Vessel Filling Operations
For vessels being filled with liquid, volatile emissions are generated from two
sources, as shown in Figure below.

Qm = Qm1 + Qm2

Qm2

Qm1
Assuming
that the
vapour is
completely
saturated
with the
volatile
Let’s,

For container vapours that

Using the ideal gas law,
It follows that rfVc is the are not saturated with the
volumetric rate of bulk volatile. Let φ
vapor being displaced from represent this adjustment
the drum (volume/time). factor; then,
Also, if ρv is the density of
the volatile vapor, rfVcρv is
the mass rate of volatile
displaced from the
container (mass/time).

For splash filling (filling from the

top of a container with the liquid
splashing to the bottom), φ = 1. For
subsurface filling (by a dip leg to the
bottom of the tank),
φ = 0.5.
The net source term resulting from filling is

The vapor concentration (in

ppm) in an enclosure resulting
from a filling operation;

Assume that T = TL
Railroad cars are being splash-filled with toluene. The 10,000-gal
cars are being filled at the rate of one every 8 hr. The filling hole
in the tank car is 4 in. in diameter. Estimate the concentration of
toluene vapor as a result of this filling operation. The ventilation
rate is estimated at 3000 ft3/min. The temperature is 77°F and the
pressure is 1 atm.
 Terima Kasih | Thank You

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